This cardiovascular research program is concerned with exploring fundamental mechanisms of cardiac contraction and their control, and coronary physiology and pathophysiology. New methods are being employed to relate directly structure and mechanics in living heart muscle in order to explain such basic characteristics of heart muscle as the length dependency of force development and resting tension. Using very small thin papillary muscle preparations, such factors as tissue inhomogeneity and branching angles between cells can now be studied as a possible basis for the large series elasticity in heart muscle. Methods are also being developed to directly measure and control groups of sarcomeres within living cardiac muscle to permit the true definition of mechanics relative to structure. The properties of the contractile and elastic elements of heart muscle are also being explored using rapid transients produced by rapid length changes with high frequency force measurements. These properties are also being related to the underlying mechanisms of excitation-contraction coupling of heart muscle. The inter-relations between coronary blood flow and myocardial function are being explored in dogs. The importance of acute and chronic collateral blood flow on the survival of cardiac tissue during acute ischemia is being elucidated. Models have been developed to define precisely the areas of myocardium involved in an acute ischemic episode and the pathophysiology and biochemistry of myocardial infarction are being studied with this model system.